Identification of a macrophage antigen-processing event required for I-region-restricted antigen presentation to T lymphocytes.
The mechanism of macrophage-antigen handling was studied using a system that involves the quantitation of the antigen-specific binding of Listeria monocytogenes-immune T cells to macrophages. Specific T cells did not bind to native antigen. Because the specific binding of T cells to macrophages could be measured during a short (5- to 15-min) interaction, it was possible to follow the temporal development of a T cell-binding substrate with increasing time of antigen-macrophage interaction. In contrast to the rapid (5-min) uptake of Listeria by macrophages, the development of T cell-binding ability required a 30- and 60-min period of antigen-macrophage interaction. During this processing period, Listeria organisms bound to the macrophage surface were ingested and partially catabolized. Unlike antigen uptake, antigen processing was a temperature-dependent and energy-requiring event. Although macrophages treated with paraformaldehyde before antigen processing did not develop T cell-binding activity, macrophages treated with paraformaldehyde after a 60-min antigen-processing period retained T cell-binding ability. The kinetics of antigen catabolism correlated with antigen processing, and inhibition of antigen catabolism was associated with a corresponding inhibition of antigen processing for T cell binding. Anti-Ia antibodies had no effect on Listeria uptake of catabolism. These results supply direct evidence for a macrophage-antigen processing event relevant to T cell recognition of antigen.
D000818:Animals; D000941:Antigens; D001665:Binding Sites; D005260:Female; D006183:H-2 Antigens; D007700:Kinetics; D008089:Listeria monocytogenes / Q000276:immunology*; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism; D008297:Male; D051379:Mice; D008805:Mice, Inbred A; D013601:T-Lymphocytes / Q000276:immunology
D000941:Antigens; D006183:H-2 Antigens